These experiments have two broad objectives. First, we intend to localize and characterize the brain sodium-receptor mechanisms involved in the central induction of changes in renal sodium excretion (U Na V) and renin secretion. Our previous dose-response studies suggest these receptors have physiological significance, especially since the changes in UNaV do not result solely from changes in blood pressure or renal mechanisms by which changes in renin and sodium excretion are brought about; our previous work on hypothalamic DI rats suggests that ADH is a likely mediator. We will therefore carry out dose-response studies comparing the natriuresis to similar plasma ADH (measured by RIA) achieved by exogenous ADH or stimulation of the Na receptors with hi-(Na). These experiments should also contribute to our kn wledge of the receptor mechanisms controling ADH secretion. Chronic effects on sodium metabolism of perfusing hi-Na or low-Na CSF will also be studied. Also, "natriuretic hormone" will be assayed. Experiments will be carried out in dogs, both anesthetized and unanesthetized, and on unanesthetized rats. The CNS mechanism of response to changes in brain sodium will be evaluated using: 1) ventriculocisternal perfusion, 2) localized push-pull perfusion in brain tissue and in ventricles, and 3) slow ventricular infusions in conscious rats. All stimulus solutions will be derived from artificial CSF. Either sodium concentrations will be changed moderately, or we will perfuse drugs which affect brain Na/K ATPase and/or intracellular (Na) to test the hypothesis that the receptor is activated by changes in membrane ATPase. We will localize the site of stimulus action via localized push-pull perfusions; the localization will also be confirmed by ablation of hypothetical receptor locations.